Enhanced phosphorylation of p53 serine 18 following DNA damage in DNA- dependent protein kinase catalytic subunit-deficient cells

Ryoko Araki, Ryutaro Fukumura, Akira Fujimori, Yoichi Taya, Yosef Shiloh, Akihiro Kurimasa, Sandeep Burma, Gloria C. Li, David J. Chen, Koki Sato, Yuko Hoki, Kouichi Tatsumi, Masumi Abe

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

DNA-dependent protein kinase (DNA-PK) controls signal transduction following DNA damage. However, the molecular mechanism of the signal transduction has been elusive. A number of candidates for substrates of DNA- PK have been reported on the basis of the in vitro assay system. In particular, the Ser-15 amino acid residue in p53 was one of the first such in vitro substrates to be described, and it has drawn considerable attention due to its biological significance. Moreover, p53 Ser-15 is a site that has been shown to be phosphorylated in response to DNA damage. In addition, crucial evidence indicating that DNA-PK controls the transactivation of p53 following DNA damage was reported quite recently. To clarify these important issues, we conducted the experiments with dna-pkcs null mutant cells, including gene knockout cells. As a result, we detected enhanced phosphorylation of p53 Ser- 18, which corresponds to Ser-15 of human p53, and significant expression of p21 and mdm2 following ionizing radiation. Furthermore, we identified a missense point mutation in the p53 DNA-binding motif region in SCGR11 cells, which were established from severe combined immunodeficient (SCID) mice and used for previous study on the role of DNA-PK in p53 transactivation. Our observation clearly indicates that DNA-PK catalytic subunit does not phosphorylate p53 Ser-18 in vivo or control the transactivation of p53 in response to DNA damage, and these results further emphasize the different pathways in which ataxia telangiectasia-mutated (ATM) and DNA-PK operate following radiation damage.

Original languageEnglish (US)
Pages (from-to)3543-3546
Number of pages4
JournalCancer research
Volume59
Issue number15
StatePublished - Aug 1 1999

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Araki, R., Fukumura, R., Fujimori, A., Taya, Y., Shiloh, Y., Kurimasa, A., Burma, S., Li, G. C., Chen, D. J., Sato, K., Hoki, Y., Tatsumi, K., & Abe, M. (1999). Enhanced phosphorylation of p53 serine 18 following DNA damage in DNA- dependent protein kinase catalytic subunit-deficient cells. Cancer research, 59(15), 3543-3546.